As a quinolinone-based compound, cilostazol (6-[4-(cyclohexyl-1H-tetrazol-5-yl)butoxy]-3,4-dihydro-2(1H)-quinolinone: Chemical formula 1) has an efficacy in controlling aggregation of blood platelets and promoting vascular relaxation by inhibiting phosphodiesterase types. Also, cilostazol is known to be useful in preventing diseases such as arteriosclerosis by suppressing the growth of vascular smooth muscle cells that have migrated to vascular endothelial cells.

Cilostazol functions to suppress the primary aggregation of blood platelets caused by ADP, epinephrine and the like in blood platelets isolated from a mouse, a rat, a rabbit, a dog and a human and dissociate a blood platelet aggregate. Also, cilostazol functions to suppress the aggregation of blood platelets induced by ADP and collagen when administered orally to a beagle, and also suppress the aggregation of blood platelets induced by ADP, collagen, arachidonic acid and epinephrine in blood platelets isolated from a patient with a chronic arterial occlusive disease (Buerger's disease, arteriosclerosis obliterans, diabetic peripheral angiopathy, etc.) when administered orally to the patient. The effect of cilostazol to suppress the blood platelet aggregation is manifested immediately after administration of the cilostazol, and maintained by repeated administration of the cilostazol. When the administration of the cilostazol is suspended, suppressed aggregation of the blood platelets returns to its original level with a decrease in its concentration in blood plasma without a rebound phenomenon (rise in aggregation).
The action mechanism of cilostazol is as follows. Cilostazol functions to suppress the release of serotonin from rabbit blood platelets, but has no effect on migration of serotonin and adenosine into the blood platelets. Also, the cilostazol functions to suppress the aggregation of blood platelets caused by thromboxane A2 (TXA2) without affecting an arachidonic acid metabolism in the blood platelets. This indicates that the cilostazol functions to inhibit cAMP-PDE (cyclic AMP phosphodiesterase) activity in blood platelets and vascular smooth muscles, thereby exhibiting an anti-blood platelet action and a vascular dilatation action.
Conventional cilostazol preparations have a disadvantage in that they have poor patient compliance when administered twice daily. Also, immediate-release cilostazol preparations have a disadvantage in that the drug is rapidly and irregularly released when administered orally. Thus, it is known that these cilostazol preparations cause side effects such as headache, heavy headedness and tachycardia with a sudden increase in cilostazol concentration in blood (see Am J Cardiol 2001; 87(suppl): 28D-33D and US 2002/0058066 A1). Since the cilostazol is poorly water-soluble and also has a reduced absorption rate in the lower small intestine, a conventional release-controlling preparation using the cilostazol has a disadvantage in that its bioavailability may be deteriorated as a whole. Also, WO 2000/57881 discloses a method of improving an absorption rate of cilostazol in the lower small intestine using a preparation in which cilostazol in a fine powder form is dispersed and/or dissolved together with a dispersing agent and/or a solubilizing agent.
Conventional cilostazol tablets cause side effects such as headache, tachycardia and heavy headedness due to a high elution rate immediately after their administration. Therefore, there is the high necessity for cilostazol prepared into a slow-release tablet, and there is a need to develop a slow-release cilostazol tablet which simply delays the release of a drug and also exhibits a stable elution rate when taken once daily.